What is the best management approach for male hypogonadism?

Management of Male Hypogonadism

Testosterone replacement therapy (TRT) is the recommended treatment for male hypogonadism, with the specific formulation choice based on patient preference, cost considerations, and risk profile. 1

Diagnosis and Evaluation

• Confirm hypogonadism with two morning fasting total testosterone measurements below the normal range
• Determine if primary (testicular) or secondary/central (hypothalamic-pituitary) hypogonadism
• Identify the most bothersome symptoms:
  • Sexual dysfunction (erectile dysfunction, decreased libido)
  • Fatigue/decreased energy
  • Decreased strength/endurance
  • Mood disturbances

Treatment Approach

When to Initiate TRT

TRT should be initiated in men with:

• Confirmed low testosterone levels
• Symptomatic hypogonadism, particularly with sexual dysfunction
• No contraindications to therapy

TRT Formulation Selection

1. Injectable testosterone (e.g., testosterone enanthate)

   • Most cost-effective option ($156.24 annual cost per Medicare beneficiary)
   • Preferred by 53% of patients primarily due to lower cost
   • Requires regular injections
   • Higher risk of fluctuating testosterone levels

2. Topical gel formulations

   • Preferred by 71% of patients who have used multiple formulations
   • More convenient, easier to use
   • More expensive ($2135.32 annual cost per Medicare beneficiary)
   • Risk of transfer to others through skin contact

Expected Benefits of TRT

• Sexual function: Small but significant improvements in erectile function and libido
• Quality of life: Small improvements
• Energy/vitality: Less-than-small improvements
• Mood: Less-than-small improvements in depressive symptoms
• Physical function: Little to no benefit
• Cognitive function: No significant improvements

Monitoring and Safety Considerations

Potential Risks and Monitoring

• Cardiovascular events: Evidence inconclusive, but caution in men with pre-existing cardiovascular disease
• Venous thromboembolism: Monitor for symptoms of DVT/PE
• Prostate health: Monitor PSA and digital rectal exam
• Polycythemia: Monitor hematocrit
• Hypercalcemia: Particularly in patients with cancer or immobilization
• Liver function: Monitor liver enzymes, particularly with oral formulations
• Edema: Monitor for fluid retention, especially in patients with cardiac, renal, or hepatic disease
• Sleep apnea: May worsen untreated sleep apnea

Contraindications to TRT

• Breast or prostate cancer
• Severe untreated sleep apnea
• Severe heart failure
• Hematocrit >54%
• Desire for fertility in the near future

Special Considerations

Fertility Preservation

For men wishing to preserve fertility, consider alternatives to standard TRT:

• Nasal testosterone (less suppression of spermatogenesis)
• Clomiphene citrate (off-label)
• Exogenous gonadotropins

Treatment Discontinuation

• TRT discontinuation rates range from 30-62%
• Consider periodic reassessment of symptoms and testosterone levels
• Long-term efficacy and safety data are limited

Pitfalls to Avoid

1. Initiating TRT without confirming low testosterone with two morning measurements
2. Expecting improvements in physical function, cognition, or energy as primary outcomes
3. Failing to monitor for adverse effects, particularly cardiovascular events and polycythemia
4. Using TRT in men actively seeking fertility
5. Not discussing the uncertain long-term safety profile with patients

TRT remains the standard of care for male hypogonadism, but treatment decisions should be guided by symptom burden (particularly sexual dysfunction), patient preferences regarding formulation, and careful consideration of potential risks.